SARS-CoV-2 Infection in Dogs and Cats: Facts and Speculations

Abstract
The recent pandemic caused by the novel human coronavirus (CoV), currently referred to as severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which is responsible for COronaVIrus Disease 2019 (COVID-19), is leading to alarmism among pet owners as a consequence of few case reports of SARS-CoV-2 infection in dogs and cats. COVID-19 emerged in December 2019 in Wuhan City, Hubei Province, China, in humans exposed to wildlife at the Huanan seafood wholesale market, the largest seafood market in central China. This is a typical Asian wet market, where different species of farm and wild animals are commonly sold dead and live. The blood and other body fluids originating from these animals represent an exceptional source for the spillover of animal viruses (1). SARS-CoV-2 recognizes a probable zoonotic origin, since the virus likely descends from a bat betacoronavirus, strictly related to the one responsible for the 2002–2003 SARS epidemic (SARS-CoV), which was transmitted to humans directly or through previous adaptation to a not yet identified intermediate host (1, 2). After this adaptation to the new host, the virus was able to spread to the human population through a human-to-human transmission, without any further role of animals in the epidemiological chain. However, pets have been alternatively brought into play as a possible source of infection for humans, intermediate hosts for SARS-CoV-2 transmission to humans or hosts of animal CoVs that may cross-protect humans against the highly pathogenic CoV. The aim of this opinion article is to define the role of dogs and cats in the SARS-CoV-2 epidemiology in the light of current knowledge. To date, sporadic cases of SARS-CoV-2 infection have been reported in dogs and cats. The first animal cases involved 2 dogs, a 17-year-old Pomeranian dog and a 2-year-old German shepherd, living in Hong Kong and in close contact with SARS-CoV-2 infected human patients (3). The animals did not display any clinical signs related to the infection and they shed, in their respiratory secretions, low SARS-CoV-2 loads as measured by real-time RT-PCR, a molecular tool able to detect even traces of viral RNA. Accordingly, a mixed breed dog living with the infected German shepherd (that also developed antibodies against SARS-CoV-2) has remained uninfected. Unfortunately, the Pomeranian dog died a few days after repeatedly testing negative for SARS-CoV-2 and the owner declined any necropsy, but the cause of death was clearly associated to the previous heart and kidney disease affecting this old animal. A third SARS-CoV-2 positive dog was later reported in North Carolina, USA. The infected pug displayed mild respiratory signs (sneeze and cough) and was living in a highly contaminated household, where 3 family members tested positive for SARS-CoV-2. The family participated in a study at Duke University that involved testing family members and their pets for COVID-191. However, the United States Department of Agriculture's National Veterinary Services Laboratories were unable to confirm the positive testing of this pug. The first confirmed case of SARS-CoV-2 infection in a pet dog in the United States was then reported in a German shepherd in the State of New York2. A greater concern was, on the other hand, generated by the involvement of cats. The first case occurred in a cat in Brussels whose owner had just returned from a vacation in Italy (4). The cat developed a gastroenteric disease. It shed discrete SARS-CoV-2 titres in the vomit and, to a lesser extent in the feces. To date, whether the observed clinical signs were associated with SARS-CoV-2 infection is unknown. Another SARS-CoV-2 infected cat was reported in Hong Kong. The pet was living with an infected human patient and did not display any clinical signs, but the virus was detected in its respiratory secretions and feces3. Two cats living in two separate areas of the State of New York and having mild respiratory illness tested SARS-CoV-2 positive. The first cat was tested after it showed mild respiratory signs, but no individuals in the household were confirmed to be ill with COVID-19. The source of infection of the cat might have been the contact with an infected human inside or outside its household. The second cat showed signs of respiratory illness after its owner tested positive for COVID-19. Both animals fully recovered from the respiratory disease (5). Sporadic cases of SARS-CoV-2 natural infection in dogs and cats were reported throughout the world (6). A high prevalence of PCR positive testing was reported in cats in Hong Kong, with 6 cases (out of 50 quarantined animals from COVID-19 positive households) of apparent human-to-feline transmission involving healthy cats (7). To date, despite these few reports of SARS-CoV-2 infections in pets, there is some evidence that cats may be more susceptible than dogs to this highly pathogenic human CoV. SARS-CoV-2 is strictly related to SARS-CoV at genetic and biological levels, being included in the same viral species, Severe acute respiratory syndrome-related coronavirus (subgenus Sarbecovirus, genus Betacoronavirus) and sharing the same cellular receptor, the angiotensin converting enzyme type 2 (ACE2) (8). SARS-CoV-2 infected cats both through the natural and the experimental routes. Several cats of the Amoy Gardens in Hong Kong, where more than 100 infected people were living, were found to be positive for SARS-CoV4 and the experimental administration of this virus resulted in a productive infection with shedding of high viral loads and virus transmission to in-contact cats (9). In-silico analysis of the feline and ferret ACE2 has shown that SARS-CoV-2 can bind with high efficiency to the receptors of these animals (10). Dogs experimentally inoculated with SARS-CoV-2 developed a mild infection and shed low titres of viral RNA. In contrast, experimentally-infected cats and ferrets appeared to be highly susceptible to SARS-CoV-2,...